OBJECTIVE:: The aim of this study was to determine the genuine prognostic relevance of primary tumor sidedness (PTS) in patients with early-stage colorectal cancer (CRC). BACKGROUND:: The prognostic relevance of PTS in early-stage CRC remains a topic of debate. Several large epidemiological studies investigated survival only and did not consider the risk of recurrence so far. METHODS:: Patients with stage II/III adenocarcinoma of the colon and upper rectum from 4 randomized controlled trials were analyzed. Survival outcomes were compared according to the tumor location: right-sided (cecum to transverse colon) or left-sided (descending colon to upper rectum). RESULTS:: A total of 4113 patients were divided into a right-sided group (N=1349) and a left-sided group (N=2764). Relapse-free survival after primary surgery was not associated with PTS in all patients and each stage [hazard ratio (HR)adjusted=1.024 (95% CI: 0.886–1.183) in all patients; 1.327 (0.852–2.067) in stage II; and 0.990 (0.850–1.154) in stage III]. Also, overall survival after primary surgery was not associated with PTS in all patients and each stage [HRadjusted=0.879 (95% CI: 0.726–1.064) in all patients; 1.517 (0.738–3.115) in stage II; and 0.840 (0.689–1.024) in stage III]. In total, 795 patients (right-sided, N=257; left-sided, N=538) developed recurrence after primary surgery. PTS was significantly associated with overall survival after recurrence (HRadjusted=0.773, 95% CI: 0.627–0.954). CONCLUSIONS:: PTS had no impact on the risk of recurrence for stage II/III CRC. Treatment stratification based on PTS is unnecessary for early-stage CRC.